Portulaca oleracea L seed extracts counteract diabetic nephropathy through SDF-1/IL10/PPARγ–mediated tuning of keap1/Nrf2 and NF-κB transcription in Sprague Dawley rats

Abstract

Abstract Background & objective : While oxidative stress is the key player driving diabetic nephropathy (DN), firm glycemic control remains the pillar prophylactic measure. Purslane was extensively described as a potent hypoglycemic and hypolipidemic agent owing to its rich content of antioxidants. Therefore, this report aimed to assess the renoprotective potentials of methanol (MO) and methylene chloride (MC) fixed oil extracts of purslane seeds in a diabetic nephropathy (DN) model. Methods Purslane seeds were extracted using absolute methanol and methylene chloride, and type-1 diabetes was induced with a single 55 mg/kg dose of Streptozotocin (STZ) dissolved in 100 mmol/L citrate buffer (pH 4.5), and then diabetic animals were received MO, MC, for 42 consecutive days to compare their antidiabetic effect relative to the reference drug “Losartan”. Renal functions and DN biomarkers were weekly assessed, and the relative expression of different oxido-inflammatory mediators was quantified in diabetic kidneys by RT-PCR. Data were statistically analyzed using GraphPad Prism 9.0.2. Results The oral administration of MO and MC extracts (250 mg/kg/day) significantly ameliorated the body weight loss (P < 0.0001 / each), fasting blood glucose levels (FBG) (P < 0.0001 / each), urine volume (P < 0.0001 / each), as well as serum creatinine (P < 0.0001 / each), uric acid (P = 0.0022, 0.0052), and blood urea nitrogen (BUN) (P = 0.0265, 0.0338); respectively, compared with the untreated diabetic rats. In addition, both extracts restored the effectuality of antioxidative machinery in diabetic kidneys as indicated by a significant reduction of ROS accumulation and lipid peroxidation; higher GSH content, and promoted activity of glutathione reductase and superoxide dismutase antioxidant enzymes (P < 0.0001 / each). Histologically, both extracts alleviated the DN-structural alterations including the glomerular congestion and tubular degeneration, with MC-treated kidneys showing near to normal architecture. The transcription profiles of all treated kidneys revealed a significantly downregulated expression of TNF-α, IL-6, Keap1 and NF-κB genes, concomitant with a significant upregulation of SDF-1, IL-10, Nrf2, HO-1, and PPARγ gene expression (P < 0.0001 / all). Conclusion These findings highlight the remarkable DN-prophylactic potentials of purslane extracts mediated by neutralizing the hyperglycemia-induced ROS accumulation, and circumventing the downstream inflammatory cascades, surpassing the reference angiotensin receptor blocker; i.e. Losartan.

Keywords

• Purslane
• Diabetic nephropathy
• Nrf2/Keap1
• PPARγ
• Oxidative stress
• Inflammation